Randomized Study of Two Chemotherapy Regimens for Treatment of Low-Grade Glioma in Young Children: A Report From the Children's Oncology Group
Division of Pediatrics, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA. Journal of Clinical Oncology
(Impact Factor: 18.43).
06/2012; 30(21):2641-7. DOI: 10.1200/JCO.2011.36.6054
PURPOSE Surgery is curative therapy for pediatric low-grade gliomas (LGGs) in areas of the brain amenable to complete resection. However, LGGs located in areas where complete resection is not possible can threaten both function and life. The purpose of this study was to compare two chemotherapy regimens for LGGs in children younger than age 10 years for whom radiotherapy was felt by the practitioner to pose a high risk of neurodevelopmental injury. PATIENTS AND METHODS Previously untreated children younger than age 10 years with progressive or residual LGGs were eligible. Children were randomly assigned to receive carboplatin and vincristine (CV) or thioguanine, procarbazine, lomustine, and vincristine (TPCV). Children with neurofibromatosis are reported separately. Results Of 274 randomly assigned patients who met eligibility requirements, 137 received CV and 137 received TPCV. The 5-year event-free survival (EFS) and overall survival (OS) rates for all eligible patients were 45% ± 3.2% and 86% ± 2.2%, respectively. The 5-year EFS rates were 39% ± 4% for CV and 52% ± 5% for TPCV (stratified log-rank test P = .10; cure model analysis P = .007). On multivariate analysis, factors independently predictive of worse EFS and OS were younger age and tumor size greater than 3 cm(2). Tumor location in the thalamus was also associated with poor OS. CONCLUSION The difference in EFS between the regimens did not reach significance on the basis of the stratified log-rank test. The 5-year EFS was higher for TPCV on the basis of the cure model analysis. Differences in toxicity may influence physician choice of regimens.
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ABSTRACT: Childhood brain tumors constitute 20–25 % of all childhood cancers diagnosed in the USA with the most common central nervous system (CNS) tumors being astrocytoma, medulloblastoma, and ependymoma. Glial tumors make up 56 % of all CNS tumors in children under the age of 14 and 45 % of all CNS tumors in adolescents. In both age groups, gliomas represent two thirds of all CNS tumors. Low-grade gliomas (LGG) include a heterogeneous group of tumors that not only have some common features, but also have characteristics that can be important for management decisions. It is important to have a multidisciplinary approach in the diagnosis and management of these young patients since most will be expected to have a long-term survival. In this article, the characteristics, diagnosis, management options, and outcomes for pediatric LGG will be reviewed.
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Pediatric low-grade glioma (LGG) is the most common brain tumor of childhood. Except for the known association of gross-total resection and improved survival rates, relatively little is known about the clinical and radiographic predictors of recurrent disease and the optimal frequency of surveillance MRI. The authors sought to determine the clinical and radiographic features associated with recurrent or progressive disease in a single-institutional series of children diagnosed with primary CNS LGG.
The authors performed a retrospective analysis of data obtained in 102 consecutive patients diagnosed at Rady Children's Hospital-San Diego between 1994 and 2010 with a biopsy-proven LGG exclusive of a diagnosis of neurofibromatosis. Tumor location, patient age, sex, and symptomatology were correlated with tumor progression or recurrence. Magnetic resonance imaging characteristics and neuroimaging surveillance frequency were analyzed in those children with progressive or recurrent disease.
Forty-six of 102 children diagnosed with an LGG had evidence of recurrent or progressive disease between 2 months and 11 years (mean 27.3 months) after diagnosis. In the larger group of 102 children, gross-total resection was associated with improved progression-free survival (p = 0.012). The location of tumor (p = 0.26), age at diagnosis (p = 0.69), duration of symptoms (p = 0.72), histological subtype (p = 0.74), sex (p = 0.53), or specific chemotherapeutic treatment regimen (p = 0.24) was not associated with tumor progression or recurrence. Sixty-four percent of children with recurrent or progressive disease were asymptomatic, and recurrence was diagnosed by surveillance MRI alone. All children less than 2 years of age in whom the tumor was diagnosed were asymptomatic at the time of progression (p = 0.04). Thirteen percent (6 of 46) of the children had disease recurrence 5 years after initial diagnosis; all of them had undergone an initial subtotal resection. Tumor progression was associated with either homogeneous or patchy T1-weighted post-Gd administration MRI enhancement in 94% of the cases (p = 0.0001).
Children diagnosed with recurrent LGG may be asymptomatic at the time of recurrence. The authors' findings support the need for routine neuroimaging in a subset of children with LGGs, even when gross-total resection has been achieved, up to 5 years postdiagnosis. The authors found that T1-weighted MR images obtained before and after Gd administration alone may be sufficient to diagnose LGG recurrence and may represent an effective strategy worthy of further validation in a larger multiinstitutional cohort.
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